The proposed studies will address first the potential efficacy of active and passive immunization for the prevention or amelioration of invasive group B streptococcal (GBS) infection in neonates by: (1) Defining the immunoglobulin isotype and IgG subclass specificity of placentally transferred antibodies to type Ia, II and III GBS polysaccharides in sera from neonates born to women with naturally-acquired or vaccine-induced antibody; (2) Determining the avidity binding of naturally-acquired or vaccine-induced GBS antibodies in human sera, and its correlation with in-vitro functional and in-vivo protective activity; (3) Comparing these characteristics of antibody acquired passively by neonates or actively by immunization of adults with that contained in human serum immune globulin (HSIG) preparations. These aims will be achieved by (1) employing a radioimmunoprecipitin assay to determine isotype specificity of antibodies, and that or an ELISA method to determine IgG subclass specificity, (2)\applying temperature-dependent antibody dissociation and competitive binding techniques to define avidity of antibody-binding for neonatal and adult sera, (3) correlating avidity binding with bactericidal activity in-vitro and protective capacity in-vivo (neonatal rat model), and (4)\defining these parameters for HSIG preparations. This should allow accurate assessment of the potential efficacy of active immunization and administration of HSIG preparations as methods for the prevention of neonatal GBS disease. The second objective of the proposal will be to delineate the opsonins mediating immunity to type II GBS by (1) correlating the concentration of type-specific anticapsular antibody, classical and alternative complement and components, and the deposition of IgG and C3b at the bacterial cell surface with efficiency of in-vitro bactericidal activity, and (2)\comparing the opsonophagocytic requirements for healthy vs. insulin-dependent adult diabetics and longitudinally (0-6 months of age) for healthy infants vs. those with II-GBS invasive infection. Addition of opsonins (HSIG and/or complement components) to sera with defined opsonic deficiencies will be performed to assess the potential usefulness of these therapeutic modalities. Finally, the prevalence of long term sequelae in four to eight year old survivors of GBS meningitis compared to their sibling controls will be determined. By comparing the objective parameters of severity of initial illness (already collected prospectively) with sequelae, factors predictive of outcome from GBS meningitis will be derived.